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The article focuses on the potential of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as a treatment for obesity and how they might fit into a comprehensive approach to managing this chronic condition. Topics include the limitations of dietary advice alone, the importance of a multi-disciplinary team approach, and the need for effective integration of GLP-1 RAs with other treatment options.

Background: Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. Methods: A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). Results: The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. Conclusions: The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug's multifaceted impact on overall metabolism in patients with obesity. [ABSTRACT FROM AUTHOR]

After bariatric surgery lifelong follow-up is recommended. Evidence of the consequences and reasons for being lost to follow-up (LTFU) is sparse. In this prospective study follow-up data of all patients who underwent bariatric surgery between 2008 and 2017 at a certified obesity centre were investigated. LTFU patients were evaluated through a structured telephone interview. Overall, 573 patients (female/male 70.9%/29.1%), aged 44.1 ± 11.2 years, preoperative BMI 52.1 ± 8.4 kg/m2 underwent bariatric surgery. Out of these, 33.2% had type 2 diabetes mellitus and 74.4% had arterial hypertension. A total of 290 patients were LTFU, of those 82.1% could be reached. Baseline characteristics of patients in follow-up (IFU) and LTFU were comparable, but men were more often LTFU (p = 0.01). Reported postoperative total weight loss (%TWL) and improvements of comorbidities were comparable, but %TWL was higher in patients remaining in follow-up for at least 2 years (p = 0.013). Travel issues were mentioned as the main reason for being LTFU. A percentage of 77.6% of patients reported to regularly supplement micronutrients, while 71.0% stated regular monitoring of their micronutrient status, mostly by primary care physicians. Despite comparable reported outcomes of LTFU to IFU patients, the duration of the in-centre follow-up period affected %TWL. There is a lack of sufficient supplementation and monitoring of micronutrients in a considerable number of LTFU patients. [ABSTRACT FROM AUTHOR]

The article discusses the issue of obesity and the current weight management services in the UK. It highlights the recent updates to the National Institute for Health and Care Excellence (NICE) guidelines, which removed the requirement for exhaustion of non-surgical measures before considering bariatric surgery. The article suggests that a community-based approach to obesity care could be a solution, with primary care and community-based multidisciplinary teams playing a significant role. It also discusses the barriers to delivering community-based obesity services, such as limited understanding of obesity management and weight bias. The article concludes that embedding specialist obesity services within primary care could expand access to much-needed services and reduce health inequalities. [Extracted from the article]

Obesity is a complex chronic disease and requires a long-term multimodal approach. The current treatment algorithm for treatment of obesity mainly consists of a stepwise approach, which starts with a lifestyle intervention followed by or combined with medication treatment, whereas bariatric surgery is often reserved for the last option. This article provides an overview of the currently available conservative medicinal treatment regimens and the currently approved medications as well as medications currently undergoing approval studies with respect to the efficacy and possible side effects. Special attention is paid to the importance of combination treatment of pharmacotherapy and surgery in the sense of a multimodal treatment. The data so far show that using a multimodal approach an improvement in the long-term weight loss and metabolic benefits can be achieved for the patients., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight., Methods and Analysis: In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18-65 years with a body mass index 30-50 kg/m 2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58-97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression., Trial Registration Number: ISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561., Competing Interests: Competing interests: Dr Miras reports grants from Fractyl, personal fees from Novo Nordisk, and personal fees from Astra Zeneka outside the submitted work. Dr Goldstone reports funding supported by UK Medical Research Council and Wellcome Trust, outside of the submitted work. Professor Poulter’s institution reports grants from HTA, during the conduct of the study. Dr le Roux reports grants from Science Foundation Ireland, grants from Health Research Board, during the conduct of the study; other from NovoNordisk, other from GI Dynamics, personal fees from Eli Lilly, grants and personal fees from Johnson and Johnson, personal fees from Sanofi Aventis, personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)